Daphnetin Alleviates Bleomycin-Induced Pulmonary Fibrosis through Inhibition of Epithelial-to-Mesenchymal Transition and IL-17A.

Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there is no cure for IPF, the development of drugs with improved efficacy in the treatment of IPF is required. Daphnetin, a natural coumarin derivative, has immunosuppressive, anti-inflammatory, and antioxidant activities. However, its antifibrotic effects have not yet been elucidated. In this study, we investigated the antifibrotic effects of daphnetin on pulmonary fibrosis and the associated molecular mechanism. We examined the effects of daphnetin on splenocytes cultured in Th17 conditions, lung epithelial cells, and a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. We identified that daphnetin inhibited IL-17A production in developing Th17 cells. We also found that daphnetin suppressed epithelial-to-mesenchymal transition (EMT) in TGF-ß-treated BEAS2B cells through the regulation of AKT phosphorylation. In BLM-treated mice, the oral administration of daphnetin attenuated lung histopathology and improved lung mechanical functions. Our findings clearly demonstrated that daphnetin inhibited IL-17A and EMT both in vitro and in vivo, thereby protecting against BLM-induced pulmonary fibrosis. Taken together, these results suggest that daphnetin has potent therapeutic effects on lung fibrosis by modulating both Th17 differentiation and the TGF-ß signaling pathway, and we thus expect daphnetin to be a drug candidate for the treatment of IPF.

A Randomized, Endoscopist-Blinded, Prospective Trial to Compare the Efficacy and Patient Tolerability between Bowel Preparation Protocols Using Sodium Picosulfate Magnesium Citrate and Polyethylene-Glycol (1 L and 2 L) for Colonoscopy.

Patient compliance during bowel preparation is important for successful colonoscopy. Bowel preparation with polyethylene glycol (PEG), the most commonly used solution for cleansing, involves the unpleasant ingestion of a large amount of liquid. Sodium picosulfate magnesium citrate (SP-MC) solution is an alternative option with better palatability than PEG. Therefore, in this study, we compared the efficacy and patient tolerability among the following three bowel preparation protocols: 2 L PEG-ascorbic acid (ASc), 1 L PEG-ASc plus bisacodyl, and SP-MC 340 mL plus bisacodyl. We conducted a randomized prospective endoscopist-blinded study between August 2018 and January 2019. A total of 311 patients were randomly classified into three groups according to the above-described bowel preparation protocols. To evaluate the efficacy of bowel cleansing, we used the Boston Bowel Preparation Scale. The degree of symptoms and the patients' satisfaction with each bowel preparation method were investigated using a questionnaire completed before sedation for colonoscopy. The baseline characteristics were similar among the three groups. There was no significant difference in the bowel preparation quality among the three groups. However, the incidence of symptoms, such as abdominal fullness and pain, was significantly lower (P = 0.006 and 0.027, respectively) while the patients' satisfaction rate was significantly higher (P = 0.012) in the SP-MC plus bisacodyl group than in the two PEG groups. In this study, the efficacy of the SP-MC plus bisacodyl solution was similar to that of the PEG solutions. However, patient tolerability and satisfaction were better in the SP-MC plus bisacodyl group than in the other groups. In conclusion, the use of SP-MC plus bisacodyl bowel preparation solution might be a better method for providing good intestinal cleansing and improving patient compliance.

Enhanced Healing of Rat Calvarial Bone Defects with Hypoxic Conditioned Medium from Mesenchymal Stem Cells through Increased Endogenous Stem Cell Migration via Regulation of ICAM-1 Targeted-microRNA-221.

The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.